# Do the expressions of HLA-G and killer cell immunoglobulin-like receptors change in colorectal cancer?

## TL;DR

This study explores how HLA-G and KIR molecules are expressed in colorectal cancer, suggesting they may help predict cancer outcomes and guide future immunotherapy.

## Contribution

The study reveals increased HLA-G and KIR expression in CRC and their variability within tumors, suggesting potential as biomarkers and therapeutic targets.

## Key findings

- HLA-G was positive in 16.7% of CRC patient samples, with no staining in controls.
- KIR positivity was significantly higher in CRC tissues compared to controls.
- KIR expression varied within the same tumor and was associated with patient age.

## Abstract

The immune system functions as a well-coordinated defense mechanism, protecting the host from both external pathogens and internal threats. Cancer cells often display surface antigens that the immune system can recognize as foreign, potentially triggering an immune response. However, many cancer cells evade detection by downregulating or completely losing these surface antigens. The immune system relies on the expression of surface antigens and human leukocyte antigens (HLA) to identify and target tumor cells. One key method by which tumor cells evade natural killer (NK) cells involves alterations in HLA antigens.

Colorectal cancer (CRC) is known to cause various changes in the immune system, including the increased expression of HLA antigens on cell surfaces, reduced functionality of NK cells, and mechanisms for immune evasion.

The aim of this study was to investigate the possible roles of innate immunity and associated HLA-G molecules in the development of CRC by examining tumor tissue samples.

We evaluated soluble HLA-G (sHLA-G) levels via ELISA, investigated HLA-G expression loss in tumor samples through immunohistochemistry (IHC), and assessed killer cell immunoglobulin-like receptor (KIR) expression on NK cells in tumor tissues.

No significant correlation was found between HLA-G and sHLA-G levels (p = 0.641). Among patient samples, 16.7% (6 of 36) were positive for HLA-G, with varying intensities, while no staining was observed in control samples. Compared to control samples, IHC staining revealed a significantly higher rate of KIR positivity in CRC tissue samples. One notable finding of our study was the variability in KIR staining intensity within the same tumor. We observed differences in KIR expression not only between tumors, but also within distinct areas of the same tumor. Additionally, a significant relationship was found between KIR expression and age.

In conclusion, this study highlights the increased expression of both HLA-G and KIR markers in CRC patients, suggesting their potential as prognostic and predictive markers. Our findings also suggest that HLA-G and KIR molecules could represent valuable therapeutic targets for future cancer immunotherapy strategies.